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TGF beta 1-induced recruitment of human bone mesenchymal stem cells is mediated by the primary cilium in a SMAD3-dependent manner

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dc.contributor.author Labour, Marie-Noëlle
dc.contributor.author Riffault, Mathieu
dc.contributor.author Christensen, Søren T.
dc.contributor.author Hoey, David A.
dc.date.accessioned 2017-01-31T09:31:10Z
dc.date.available 2017-01-31T09:31:10Z
dc.date.issued 2016
dc.identifier.uri http://hdl.handle.net/10344/5482
dc.description peer-reviewed en_US
dc.description.abstract The recruitment of mesenchymal stem cells (MSCs) is a crucial process in the development, maintenance and repair of tissues throughout the body. Transforming growth factor-β1 (TGFβ1) is a potent chemokine essential for the recruitment of MSCs in bone, coupling the remodelling cycle. The primary cilium is a sensory organelle with important roles in bone and has been associated with cell migration and more recently TGFβ signalling. Dysregulation of TGFβ signalling or cilia has been linked to a number of skeletal pathologies. Therefore, this study aimed to determine the role of the primary cilium in TGFβ1 signalling and associated migration in human MSCs. In this study we demonstrate that low levels of TGFβ1 induce the recruitment of MSCs, which relies on proper formation of the cilium. Furthermore, we demonstrate that receptors and downstream signalling components in canonical TGFβ signalling localize to the cilium and that TGFβ1 signalling is associated with activation of SMAD3 at the ciliary base. These findings demonstrate a novel role for the primary cilium in the regulation of TGFβ signalling and subsequent migration of MSCs, and highlight the cilium as a target to manipulate this key pathway and enhance MSC recruitment for the treatment of skeletal diseases. en_US
dc.language.iso eng en_US
dc.publisher Nature Publishing Group en_US
dc.relation.ispartofseries Scientific Reports;6: 35542
dc.subject in-vitro en_US
dc.subject intraflagellar transport en_US
dc.subject migration en_US
dc.subject expression en_US
dc.title TGF beta 1-induced recruitment of human bone mesenchymal stem cells is mediated by the primary cilium in a SMAD3-dependent manner en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2017-01-30T15:14:07Z
dc.description.version PUBLISHED
dc.identifier.doi 10.1038/srep35542
dc.contributor.sponsor ERC en_US
dc.contributor.sponsor SFI en_US
dc.relation.projectid 336882 en_US
dc.relation.projectid 13/ERC/L2864 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2691544
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Scientific Reports
dc.description.status peer-reviewed


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